We are characterizing in biochemical terms the elements of the skeletal framework and their function. One such function is attachment of polyribosomes via mRNA, which appears obligatory for translation; the 25% of cellular poly A plus mRNA free of the skeleton is not active. The polyribosomes are attached at specific locations in the skeleton and assembly of the skeleton is associated closely in time and space to the synthesis of skeletal proteins. The skeleton is also the site of VSV virus replication, message production and assembly. We are also exploring the relationship between the skeleton and gene expression. In 3T6 cells, protein synthesis requires simple contact, while nuclear events such as rRNA and DNA synthesis require cell spreading. In a cell series from diploid fibroblasts to fully transformed, additional levels of macromolecular metabolism lose regulation by attachment with transformation. In parallel, the same series viewed by TEM in whole mount shows increasing disorganization with transformation. Equally extensive reorganization can occur under cellular control, as muscle cells become transiently unstable immediately before fusion and rapidly reorganize afterwards, thus showing three states of organization during two days' development.